1. The New Surviving Sepsis Bundles: From Time Zero to Tomorrow
R. Phillip Dellinger, MD, MCCM
Mitchell M. Levy, MD, FCCM

2. Faculty R. Phillip Dellinger, MD, MCCM Professor of Medicine
Cooper Medical School of Rowan University
Director, Critical Care
Cooper University Hospital
Camden, NJ
2004, 2008 & 2012 SSC Guidelines Co-Chair
SCCM SSC Steering Committee
Past President, SCCM

3. NEW sepsis bUNDLES R. Phillip Dellinger MD, MSc, MCCM
Professor of Medicine
Cooper Medical School of Rowan University
University Medicine and Dentistry of New Jersey
Director Critical Care Medicine
Cooper University Hospital
Camden NJ USA
The initial resuscitation of the patient is of utmost importance and frequently occurs in the emergency department or on hospital wards.

4. Potential Conflicts of Interest
No direct or indirect potential financial conflict of interest as to any material presented in this presentation

5. SURVIVING SEPSIS CAMPAIGN BUNDLES
TO BE COMPLETED WITHIN 3 HOURS: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L TO BE COMPLETED WITHIN 6 HOURS: 5) Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure [MAP] 65 mm Hg) 6) In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate ≥ 4 mmol/L (36 mg/dL): - Measure central venous pressure (CVP)* - Measure central venous oxygen saturation (ScvO2)* 7) Remeasure lactate if initial lactate was elevated* *Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg, ScvO2 of 70%, and normalization of lactate

6. Why measure lactate?

7. Why measure lactate?
Diagnose severe sepsis with elevated lactate as a diagnosis of tissue hypoperfusion
Trigger for quantitative resuscitation if lactate is 4 mg/dL or more

8. SURVIVING SEPSIS CAMPAIGN BUNDLES
TO BE COMPLETED WITHIN 3 HOURS: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L TO BE COMPLETED WITHIN 6 HOURS: 5) Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure [MAP] 65 mm Hg) 6) In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate ≥ 4 mmol/L (36 mg/dL): - Measure central venous pressure (CVP)* - Measure central venous oxygen saturation (ScvO2)* 7) Remeasure lactate if initial lactate was elevated* *Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg, ScvO2 of 70%, and normalization of lactate

9. Blood Cultures

10. Diagnosis
To optimize identification of causative organisms, we recommend at least two blood cultures be obtained before antimicrobial therapy is administered as long as such cultures do not cause significant delay (>45 minutes) in antimicrobial administration, with at least one drawn percutaneously and one drawn through each vascular access device, unless the device was recently (<48 hr.) inserted (Grade 1C).

11. SURVIVING SEPSIS CAMPAIGN BUNDLES
TO BE COMPLETED WITHIN 3 HOURS: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L TO BE COMPLETED WITHIN 6 HOURS: 5) Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure [MAP] 65 mm Hg) 6) In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate ≥ 4 mmol/L (36 mg/dL): - Measure central venous pressure (CVP)* - Measure central venous oxygen saturation (ScvO2)* 7) Remeasure lactate if initial lactate was elevated* *Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg, ScvO2 of 70%, and normalization of lactate

12. Time to Antibiotics Following Onset Septic Shock
Kumar A, et al. Crit Care Med 2006; 34:

13. Antibiotic Therapy
We recommend that intravenous antibiotic therapy be started as early as possible and within the first hour of recognition of septic shock (1B) and severe sepsis without septic shock (1C).
Remark: Although the weight of evidence supports prompt administration
of antibiotics following the recognition of severe sepsis and septic shock, the feasibility with which clinicians may achieve this ideal state has not been scientifically validated.

14. Antibiotic Therapy
Initial empiric anti-infective therapy – activity against all likely pathogens and adequate concentrations into suspected or potential sources of infection (1B)
Reassess antibiotic regimen daily for de-escalation (1B)

15. SURVIVING SEPSIS CAMPAIGN BUNDLES
TO BE COMPLETED WITHIN 3 HOURS: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L TO BE COMPLETED WITHIN 6 HOURS: 5) Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure [MAP] 65 mm Hg) 6) In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate ≥ 4 mmol/L (36 mg/dL): - Measure central venous pressure (CVP)* - Measure central venous oxygen saturation (ScvO2)* 7) Remeasure lactate if initial lactate was elevated* *Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg, ScvO2 of 70%, and normalization of lactate

17. Fluid therapy
Crystalloids (1B)
Albumin (2C)
Avoid HES (1B)

18. Meta-Analysis
Delaney AP, Dan A, McCaffrey J, et al: The role of albumin as a resuscitation fluid for patients with sepsis: A systematic review and meta-analysis. Crit Care Med 2011; 39:386–391

19. Fluid therapy
Initial fluid challenge in sepsis-induced tissue hypoperfusion (hypotension or elevated lactate) with suspicion of hypovolemia to be a minimum of 30ml/kg of crystalloids(a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid, may be needed in some patients ( 1B)

20. SURVIVING SEPSIS CAMPAIGN BUNDLES
TO BE COMPLETED WITHIN 3 HOURS: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L TO BE COMPLETED WITHIN 6 HOURS: 5) Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure [MAP] 65 mm Hg) 6) In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate ≥ 4 mmol/L (36 mg/dL): - Measure central venous pressure (CVP)* - Measure central venous oxygen saturation (ScvO2)* 7) Remeasure lactate if initial lactate was elevated* *Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg, ScvO2 of 70%, and normalization of lactate

21. Resuscitation of Sepsis Induced Tissue Hypoperfusion
Recommend MAP 65 mm Hg
Grade 1C

22. Vasopressors

23. During Septic Shock Diastole Systole 10 Days Post Shock
This slide demonstrates radionuclide angiography in a patient during septic shock and following recovery. The top left panel shows end-diastole and demonstrates increased diastolic size of the ventricles (increased compliance), which is thought to be an adaptive mechanism. The top right image shows end-systole in this patient demonstrating a very low ejection fraction (little change in chamber size compared to end-diastole). The bottom two frames following recovery demonstrate a decrease in end-diastole volume, smaller ventricle at end systole and therefore significant improvement in ejection fraction.

24. 28-day Survival
De Backer D, et al. N Engl J Med 2010, 362;9:

25. Predefined subgroup analysis by type of shock
De Backer D, et al. N Engl J Med 2010, 362;9:

26. Meta-analysis – NE versus dopamine
Crit Care Med. 2012 Mar;40(3):725-30

27. Vasopressors Front line: (1) Norepinephrine (1B). (2) Epinephrine (2B)
Vasopressin .03 units/min (UG)

28. Vasopressors In general avoid Dopamine, unless
Relative or absolute bradycardia and low risk of tachyarrhythmias
(2C)
Phenylephrine, unless
Norepinephrine associated with serious arrhythmias
Cardiac output is known to be high and blood pressure target difficult to achieve
As salvage therapy
(1C)

29. Sepsis Induced Tissue Hypoperfusion
Requirement for vasopressors after fluid challenge
Lactate ≥ 4 mg/dL
The initial resuscitation of the patient is of utmost importance and frequently occurs in the emergency department or on hospital wards.

30. Quantitative Resuscitation
Critical Care Medicine. 36(10):

31. Protocolized
Care

32. SURVIVING SEPSIS CAMPAIGN BUNDLES
TO BE COMPLETED WITHIN 3 HOURS: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L TO BE COMPLETED WITHIN 6 HOURS: 5) Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure [MAP] 65 mm Hg) 6) In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate ≥ 4 mmol/L (36 mg/dL): - Measure central venous pressure (CVP)* - Measure central venous oxygen saturation (ScvO2)* 7) Remeasure lactate if initial lactate was elevated* *Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg, ScvO2 of 70%, and normalization of lactate

33. Initial Resuscitation of Sepsis Induced Tissue Hypoperfusion
Recommend
Insertion central venous catheter
Recommended goals :
Central venous pressure: 8–12 mm Hg
Higher with altered ventricular compliance or increased intrathoracic pressure
ScvO2 saturation (SVC)  70%
Grade 1C

34. Limitation of pressure measurement to predict fluid responsiveness

35. Arterial Systolic Pressure Variation
Parry-Jones, et al. Int J Respir Crit Care Med 2003;2:67

36. Effect on Cardiac Filling

37. Effect on Stroke Volume
Part A
Once the initial Arterial thermodilution Cardiac Output is obtained the system is now calibrated to do the PCCO measurement.
PCCO is the measurement of Continuous Cardiac Output which is measured beat to beat.
How many of you look at the arterial line wave form to determine if the patient has adequate vascular volume ?
Tall narrow and peaked waveform may be an indication of possible hypovolemia.
Wide and Fat may be an indication of low vascular volume.
The truth is that the area under the arterial wave form is proportional to stroke volume. We determine the stroke volume and multiply it buy the heart rate and get Cardiac Output. t

38. Effect on Stroke Volume

40. SURVIVING SEPSIS CAMPAIGN BUNDLES
TO BE COMPLETED WITHIN 3 HOURS: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L TO BE COMPLETED WITHIN 6 HOURS: 5) Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure [MAP] 65 mm Hg) 6) In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate ≥ 4 mmol/L (36 mg/dL): - Measure central venous pressure (CVP)* - Measure central venous oxygen saturation (ScvO2)* 7) Remeasure lactate if initial lactate was elevated* *Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg, ScvO2 of 70%, and normalization of lactate

41. Lactate Clearance
In patients with elevated lactate levels as a marker of tissue hypoperfusion we suggest targeting resuscitation to normalize lactate as rapidly as possible (grade 2C).

43. Thank You

44. QUESTIONS?